PROMYSE

Products from methanol by synthetic cell factories

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 Obiettivo del progetto (Objective)

There is a high societal need for a sustainable production of key chemistry, food and health care compounds. Microbial cell factories are logical production systems, but up to now they use sugars and other food derived raw materials as substrates. Sugars originating from plants demand cultivable land which is more and more needed for human nutrition. Methanol - with a worldwide production capacity of more than 46 million tons per year - is regarded as an alternative highly attractive raw material in microbial fermentation for the manufacturing of special, fine, bulk, and fuel chemicals. This is especially true for the EU market, where industrial biotechnology still is hampered by strict use and price regulations as well as import limitations for agricultural commodities, such as corn or sugar. The supply of methanol can base upon both fossil and renewable resources, rendering it a highly flexible and sustainable raw material. Our vision is a viable methanol-based European bio-economy, which we will promote by for the first time applying synthetic biology principles for cell factory development in order to harness methanol as a general feedstock for the manufacturing of special and fine chemicals. In nature, methylotrophic microorganisms can utilize methanol as their sole source of carbon and energy. The project PROMYSE will deliver an alternative route to sought-after chemicals, with a major focus on terpenoids. PROMYSE combines two frontline research topics: orthogonal modularization of methylotrophy within a Synthetic Biology concept and employing methanol as a feedstock for biotechnological production. Through the transfer of methylotrophy modules, Synthetic Biology will pave the way to capitalize on the metabolic versatility and engineered production pathways of genetically well tractable microorganisms, such as E. coli, B. subtilis and C. glutamicum for biotransformation from methanol.

Introduzione (Teaser)

Microbial cell factories are logical production systems that use sugars and other food-derived raw materials as substrates. Microbial utilisation of methanol for biotechnological production of chemicals is a promising sustainable alternative.

Descrizione progetto (Article)

Methanol is regarded as a very desirable alternative raw material in microbial bioprocesses. The supply of methanol is based on both fossil and renewable resources, rendering it a highly flexible and sustainable raw material. However, methylotrophic (methanol-based) bacteria typically lack certain favourable traits necessary for industrial application as microbial cell factories.

The EU-funded 'Products from methanol by synthetic cell factories' (http://www.sintef.no/Projectweb/PROMYSE/ (PROMYSE)) consortium is working on engineering methylotrophy in non-methylotrophic bacteria using synthetic biology concepts. For biotechnological production, PROMYSE combined orthogonal modularisation of methylotrophy and harnessing of methanol as general feedstock.

Synthetic biology strategies combined engineering and testing with predictions and modelling to generate novel methylotrophs. Major achievement of the project was proof of possibility to generate valuable products from methanol using well established biotechnologically relevant hosts. At the final step, researchers used labelled methanol and demonstrated that the newly constructed recombinant strains could consume and incorporate methanol into cell constituents.

Partners of PROMYSE biochemically characterised six different methanol dehydrogenases and their activator proteins. To incorporate methylotrophy, they transferred each of them to the three selected non-methylotrophic hosts. They have constructed recombinant Bacillus methanolicus (Bm) strains that produce important platform chemical used in production of bioplastics, from methanol.

The results of the project were presented so far in many publications and patents. Together, the generated knowledge will be important for future utilisation of methylotrophic bacteria for sustainable production of a variety of compounds.